Project Summary This proposal seeks to acquire an optical sectioning commercial microscope to be housed in the Edwards Lifesciences Center for Advanced Cardiovascular Technology (ELCACT). The confocal microscope will have two-photon imaging capabilities and on-stage incubation for longitudinal studies. The features of the microscope will greatly aid the research efforts of UCI scientists who have enthusiastically joined the proposal to share the instrument. The proposed major and minor users perform research in the areas of cardiac tissue engineering (Grosberg, Downing), vascularized heart-on-a-chip platform for drug screening (Hughes, Lee), development of clinical nonlinear imaging devices (Chen), mechanobiology (Botvinick), cellular self-assembly (Grosberg), cardiac valve tissue engineering (Kheradvar), orthopedic tissue engineering (Athanasiou), and immunomodulation for cardiovascular implant compatibility (Liu). The proposed instrument will aid the users' NIH funded research in multiple ways. For instance, the microscope will enable deep imaging of de novo tissues, which will allow quantification of extracellular matrix structure and content (Hughes, Botvinick, Grosberg, Athanasiou, Kheradvar), vascular architecture and protein expression (Hughes, Botvinick), myofibril architecture (Grosberg, Downing), and immune cell phenotype (Liu). While a few non-linear confocal microscopes can be found within shared facilities at UCI, these are impacted are cannot accommodate the volume of experiments conducted by the major and minor users in the proposal. Further, common to the research of many users is longitudinal culture of environmentally-sensitive tissues that cannot be transported out of the building without compromising the experiments. The proposed instrument will be housed directly across the hall from the ELCACT Core Tissue Culture Facility and proximal to the individual laboratories of major and minor users, which will mitigate this risk and bring a set of capabilities to the center to accelerate research. There is a self-sustaining financial plan comprising a ELCACT resources commitment, and substantial institutional commitment. Specifically, in support of this application, ELCACT is providing both space and support staff for this system, while the Office of the Research is committed to paying for the full service and training contract through year five. In summary, the financial plan will ensure that the system is maintained through both an extended service agreement, augmented by the expertise of the PI in laser scanning microscopes and the appropriate ELCACT staff. The proposed instrument will provide new capabilities and enhance NIH funded research at the University of California Irvine School of Engineering.